双氟沙星在人工感染嗜水气单胞菌的异育银鲫体内的药代动力学
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国家863计划项目(No.2011AA10A216),公益性行业(农业)科技专项资金项目(No.201203085),现代农业产业技术体系建设专项资金项目(No.CARS-46-12)


Pharmacokinetics of Difloxacin in the Aeromonas hydrophila-infected Carassius aurutus gibelio
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    摘要:

    为了阐明双氟沙星在健康与处于患病状态下的异育银鲫(Carassius aurutus gibelio)体内的药代动力学特征差异,为双氟沙星的正确合理用药提供参考,本研究通过人工创伤感染的方式采用最佳浓度的嗜水气单胞菌(Aeromonas hydrophila)感染异育银鲫,在此基础上进一步以双氟沙星在健康异育银鲫体内的药代动力学特征为对照,采用反相高效液相色谱法测定双氟沙星在感染嗜水气单胞菌的异育银鲫体内的药代动力学特征。实验结果表明,以鱼体重的20 mg/kg口灌给药后,双氟沙星在人工感染嗜水气单胞菌的异育银鲫与健康异育银鲫体内的总药时曲线均符合一级吸收开放性二室模型,其药动学方程分别为C=6.227e-0.109t-8.074e-2.752t+1.847e-0.006tC=110.295e-0.331t+1.533e-0.01t-111.828e-0.412t,但与双氟沙星在健康异育银鲫体内的药代动力学参数相比,双氟沙星在人工感染嗜水气单胞菌的异育银鲫体内的吸收、分布、消除速度减慢,其在人工感染嗜水气单胞菌的异育银鲫体内的分 布半衰期、消除半衰期、吸收速率常数、曲线下面积分别增加了4.25 h、36.17 h、2.34/h和74.52 mg·h/L,达峰时间延长了5.75 h,峰浓度降低了61.16%,且未出现重吸收现象。本研究证实嗜水气单胞菌感染能够导致异育银鲫肝肾功能损伤,因而双氟沙星在人工感染嗜水气单胞菌的异育银鲫体内的吸收、分布、代谢和消除均会减慢。

    Abstract:

    In order to clarify the difference in the pharmacokinetic parameters of difloxacin in diseased and healthy Carassius aurutus gibelio and to provide the scientific data for the rational use of difloxacin, C.a.gibelio was infected in wound with the optimal concentration of Aeromonas hydrophila. The pharmacokinetic parameters of difloxacin in the diseased C.a.gibelio were tested through an established reversed-phase high performance liquid chromatography method, and data were compared to those obtained from the healthy control C.a.gibelio. The results showed that the concentration-time curves of difloxacin orally administered at a dose of 20 mg/kg body weight in the diseased and healthy C.a.gibelio were both in accordance with the first order absorption and open two-compartment models. The pharmacokinetic equations were C=6.227e-0.109t-8.074e-2.752t+1.847e-0.006t and C=110.295e-0.331t+1.533e-0.01t-111.828e-0.412t, respectively. However, compared to the pharmacokinetic parameters of difloxacin in the healthy C.a.gibelio, the difloxacin's absorption, distribution and elimination speeds in the diseased C.a.gibelio were reduced. The distribution half-life, elimination half-life, absorption rate constant, area under a curve of difloxacin in the diseased C.a.gibelio were increased by 4.25 h, 36.17 h, 2.34/h and 74.52 mg·h/L, respectively, and its time on the break point was extended 5.75 h, its peak of plasma concentration was decreased by 61.16% and its reabsorption disappeared. The present study confirmed that the liver and kidney functions of C.a.gibelio could be damaged by A.hydrophila infection, and the absorption, distribution and elimination of difloxacin in the diseased C.a.gibelio could be slowed.

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章海鑫,曹海鹏,阮记明,胡鲲,杨先乐.2012.双氟沙星在人工感染嗜水气单胞菌的异育银鲫体内的药代动力学.动物学杂志,47(6):72-77.

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  • 收稿日期:2012-05-15
  • 最后修改日期:2012-07-05
  • 在线发布日期: 2012-12-19